The primary structure of fragments obtained by cleavage of human fibrinogen with CNBr and plasmin are at present being studied. Of particular interest are the polypeptide chains of fragment D (M.W. 100,000) and an early COOH-terminal plasmic fragment of the A alpha chain (M.W. 50,000). Structural studies are also being performed on CNBr fragments linking the A alpha and B beta chains of fragment E with the corresponding chains in fragment D. The disulfide bridges in fragment D will be elucidated by studies of disulfide-fragments obtained from fragment D by cleavage with CNBr. The antigenic structure of fibrinogen is under investigation, using isolated chains, fragments of the molecule, and antibodies to these structures. Radioimmune systems and cross-immunoelectrophoretic methods are used. Efforts are made to identify molecular structures involved in polymerization of fibrinogen, by studying the effect of selective labelling of critical amino acid residues, and the "polymerization" inhibition of various fragments of the molecule. On oxidation of partially reduced fibrinogen, renaturation occurs. The disulfide bonds critical for polymerization are being explored. Disulfide exchange reactions in cross-linkage of fibrin are also being investigated. Specificity of thrombin and thrombin-like enzymes is studied on different substrates obtained from the A alpha and B beta chain. Methods for determination of thrombin, other blood coagulation factors and their inhibitors by spectrophotometic analyses, using synthetic substrate are being elaborated.